On the Shoulders of Giants: One Scientist’s Diabetes Research Journey

By the start of the 1920s, a treatment for diabetes, one of the world’s oldest diseases, had eluded the medical community for over two millennia. However, the prolonged wait was nearly at an end. In 1921, a research team from the University of Toronto isolated a new hormone from dogs. That hormone was insulin, the body’s regulator of blood glucose (sugar) levels. A year later, Indianapolis’ own Eli Lilly began mass-producing purified insulin for public use, transforming diabetes from a death sentence to a chronic disease.  While this Nobel Prize winning discovery revolutionized the way diabetes was treated, it was not a definitive cure. For the time being, the quest to understand one of the world’s oldest diseases continued.

A Growing Epidemic

Although diabetes is one of the most prevalent diseases in the world, with 26.9 million diagnosed individuals in the United States alone (8.2% of the population), few members of the public understand exactly how the disease develops. In short, diabetes develops when the body is unable to properly manage its blood glucose (sugar) levels, resulting in an excess of sugar in the blood. Normally, blood glucose is tightly regulated by insulin-producing beta cells found within the pancreas, a yellow, 5-6 in. long, multi-lobed organ located behind the stomach. However, in patients with diabetes, these pancreatic beta cells lose their ability to produce or recognize insulin, causing the body to lose its ability to manage its own blood glucose. In the case of Type I diabetes, the insulin-producing beta cells are destroyed by the body’s own immune cells, preventing it from producing adequate amounts of insulin. This form is more commonly diagnosed in children and young adults and currently has no known method of prevention. Type 2 diabetes develops when the body becomes insensitive to insulin after blood glucose levels remain consistently elevated for long periods of time. This form of diabetes  comprises 90-95% of diabetes cases and is mostly diagnosed in adults, although cases in children and young adults have been increasing significantly due to unhealthy lifestyles. Both forms of diabetes manifest with a variety of common symptoms such as extreme hunger, extreme thirst, excessive urination, exhaustion, and blurry vision. If left unchecked, these symptoms can rapidly lead to death.

A Giant Step Forward

Prior to the discovery of insulin therapy, diabetes treatments were limited and did little to halt the progression of the disease. Similar to modern times, physicians prescribed calorie- and sugar-restricted diets and exercise to curtail the progression of the disease. In the past, however, these restrictive diets often kept patients at the point of starvation, sometimes only allowing as little as 450 calories a day (for reference, a single Chick-fil-A chicken sandwich is 440 calories). This method of treatment was particularly heartbreaking for young patients with Type 1 diabetes who desperately needed the nutrition for their growth. Even when patients with diabetes were able to adhere to these stringent diets and survive daily starvation, their efforts only prolonged their austere lives by a few short years. With the introduction of insulin, blood sugar levels and thus diabetes could be regulated more thoroughly through careful glucose monitoring and regular injections of insulin. Over the years, new advances such as automated insulin pumps have made the administration and regulation of insulin even easier, but the underlying principle remains the same.

Following in Their Footsteps

Now, as the 100th anniversary of insulin therapy approaches, Dr. Teresa Mastracci, Ph.D., is striving to make similar strides with her own research. While earning her Ph.D. from the University of Toronto, Mastracci developed a passion for scientific research involving developmental biology, cancer, and diabetes, leading her to complete postdoctoral studies at Columbia University and the Naomi Berrie Center for Diabetes Research in New York. In search of a research community where she could then establish her independent lab, Mastracci was drawn to Indiana University – Purdue University Indianapolis and Indiana University School of Medicine.

Now an Assistant Professor of Biology and Adjunct Assistant Professor of Biochemistry & Molecular Biology, Dr. Mastracci and her lab investigate how organs form in the hopes that it will provide insight into how non-functional organs can be revived or replaced. More specifically, the Mastracci lab is looking to restore the insulin-producing beta cells that are lost in the pancreas of individuals with diabetes. To conduct their research, Mastracci’s lab performs experiments using animal models such as mice and zebrafish. In one recently published study, the Mastracci lab found that an FDA-approved drug known as difluoromethylornithine (DFMO) promoted beta cell regrowth in zebrafish.

However, Mastracci cautioned that reviving dying beta cells and restoring their insulin functions for patients with diabetes, a process known as cellular regeneration, is easier said than done. Unlike its sensationalized portrayal in popular media such as Grey’s Anatomy, cellular regeneration will require significant time and research to fully understand and develop into a safe, effective diabetes treatment. While the journey from promising preliminary results to effective therapeutic will require more than just this one study, Mastracci’s research may provide interesting insights into cell regeneration as a treatment for diabetes.

Those Who Come Before and After

When discussing advances in diabetes research and treatments, Mastracci noted, “discoveries don’t happen in isolation, but rather stem from previous work.” Every advance in research is built upon both the successes and the failures of the scientists that came before. To that end, Mastracci is an incredible advocate for science communication and outreach, particularly with K- 12 students. In her view, these students represent the future of science and may one day pick up the torch and continue her work in the diabetes research field. On her school outreach visits, Mastracci brings along scientific tools from her lab to help explain how experiments are performed. Sparking the students’ interest in this manner and introducing them to the field is one of Mastracci’s most rewarding experiences and it keeps her coming back to interact with the students again and again.

Mastracci’s outreach activities also aren’t confined to the laboratory or the classroom. As part of her work with the Juvenile Diabetes Research Foundation (JDRF), a nonprofit organization dedicated to funding Type I diabetes research and serving those affected by Type I diabetes, Mastracci often participates in fundraising events such as the JDRF Ride to Cure Diabetes. At these events, Mastracci and other researchers, clinicians, patients, and family members strap on their bicycle helmets and cycling shoes to raise funds for Type I diabetes research.

Although Mastracci and fellow researchers like her are making significant strides towards our understanding of diabetes progression and treatment, there is still much more work to be done. If you would like to learn more about Mastracci’s diabetes research, you can read her publications here. If this is a cause you are interested to support, you can donate here to one of the non-profit organizations that fund critical diabetes research.

Andrew S. Cale, MS is a doctoral candidate in Anatomy Education at Indiana University School of Medicine, Indianapolis, IN. He teaches gross anatomy to medical, allied health, and graduate students and his research interests include anatomy education, metacognition, and science communication. You can learn more about his work at www.caleanatomy.com or connect with him on Twitter at @Drewboo830.